Abstract

Introduction Influenza vaccination prevents substantial morbidity, and mortality, and the spread of infection, but patients still sometimes
refuse vaccinations due to concerns over adverse reactions. Our aim was to determine the relative risk of COPD exacerbations
post-vaccination.

Methods We analysed data before and after 162 vaccinations given to 112 patients in the London COPD cohort between 2009 and 2011.
Patients recorded on daily diary cards increase in respiratory symptoms. Exacerbations were defined as ≥2 days of 2 major
symptoms (new or increased breathlessness, sputum volume or purulence) or 1 major and 1 minor symptom (cold, increased cough,
increased wheeze, sore throat). Patients were telephoned in Oct 2011 and asked about recent or forthcoming vaccinations; other
dates were known from previous years when recorded diary cards or reported at clinic visits.

The risk of COPD exacerbation in the two post-vaccination periods, days 1–2 and 3–14 were calculated relative to the patient’s
baseline risk assessed over the year before and after vaccination using a self-controlled case series approach. The data was
also simply analysed with a Chi-squared test of the proportion of exacerbations in the two weeks before and after vaccination.

Results There was a 3.31 fold (95% CI 1.5–7.4; P=0.004) increased risk of COPD exacerbation 1–2 days post influenza vaccination,
and a 1.8 fold risk (1.2–2.9; p=0.007) 3–14 days afterwards. In the two weeks prior to vaccination there were 5/162 exacerbations
and 26/162 in the two weeks post vaccination (p<0.001). All 5 of the exacerbations before and 17/26 exacerbations after vaccination
were treated with antibiotics and/or oral steroids. Using thie healthcare utilisation definition of COPD exacerbations, there
were still significantly more events post vaccination (p=0.008). Figure 1 shows the average number of new or increased respiratory symptoms recorded by the patients during the 3 weeks before and
after vaccination.

Conclusion The incidence of COPD exacerbation increases immediately after influenza vaccination. COPD patients should be warned about
increased respiratory symptoms after their influenza vaccination. Future studies should investigate the mechanisms underlying
these increased symptoms in order to intervene and prevent them effectively.